Abstract
Angiogenesis, the generation of new blood vessels from a previously existing vasculature, is reinforced by the dynamic migration and signaling of wrapping support cells, termed pericytes, covering the capillary endothelium. Understanding pericyte‐endothelial cell interactions involved in angiogenesis is essential for developing therapies targeted at improving blood vessel growth and stabilization during disease, such as in diabetic wound healing. Previous work has established a connection between diminished pericyte coverage and delayed angiogenesis in diabetic wound healing models. To date, the location and identity of pericytes in healthy versus diabetic angiogenic networks has yet to be explored. Therefore, the objective of this study is to compare the extent of pericyte coverage in angiogenic networks of diabetic versus healthy mice.Adult female heterozygous Ins2(Akita) diabetic mice and wild type mice (n=6 per group) underwent a silver nitrate chemical burn on the surface of the eye to induce corneal angiogenesis. Angiogenic sprouting into the previously avascular tissue was imaged daily using bright field microscopy. Three and seven‐days after injury, corneas were harvested and stained with CD31 (endothelial cell marker), NG2 (pericyte marker), and myosin heavy‐chain 11 (Myh11, pericyte and smooth muscle cell marker).Using whole‐mount confocal imaging, Myh11+, NG2+ perivascular coverage over CD31+ endothelial cells was quantified in the vascular areas of the mouse models. There was a negative correlation between overlapping coverage of the two pericyte markers and glucose concentration (mg/dL) at days three and seven post‐stimulation (r‐square= 0.888 and 0.893, respectively). Subconjuctival hemorrhages per tissue in diabetic models were increased by 3.64‐fold and 4.00‐fold after three and seven days between glucose level and number of hemorrhages (r‐square= 0.787 and 0.831, respectively).Diabetic neovessels in this injury model have diminished pericyte coverage relative to healthy mice, which is consistent with the presence of abundant subconjuctival hemorrhages in diabetic corneas. The comparison between data collected and glucose concentration in the blood is essential to understanding the relationship between these readings with the severity of diabetic effects, with an increase in glucose concentration equating to a decrease in pericyte‐supported vasculature. Together, these data suggest that reduced pericyte coverage on neovessels may contribute to the impaired angiogenesis that occurs during diabetic wound healing.Support or Funding InformationUniversity of Virginia Vice President for Research, Harrison Foundation, and the Arnold and Mabel Beckman Foundation
Published Version
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